Chapter 20 Systemic Mycoses
The four classical systemic mycoses of dogs and cats are histoplasmosis, blastomycosis, coccidioidomycosis, and cryptococcosis.
Fungal infections with a predilection for individual organ systems are discussed elsewhere; thus, for deep cutaneous fungal infections see Chapter 40, for dermatophytosis see Chapter 42, for intestinal pythiosis see Chapter 69, and for nasal aspergillosis see Chapters 160 and 163.
Histoplasmosis, blastomycosis, and coccidioidomycosis are endemic to defined regions of North America (Fig. 20-1).
HISTOPLASMOSIS
Etiology
• Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic soil-dwelling fungus found in many temperate and subtropical regions of the world. In North America, the disease is most prevalent in the river valley regions of the central United States, especially in areas bordering the Mississippi, Ohio, and Missouri Rivers and their tributaries (see Fig. 20-1). Both dogs and cats are susceptible.
• At ambient temperatures, soil enriched by decomposing nitrogenous matter (e.g., bird feces or bat guano) provides an ideal growth medium for the mycelial phase of Histoplasma. The principal route of infection is by inhalation of airborne spores (conidia) and mycelial fragments in windblown soil; however, intestinal infection via ingestion also may occur. At body temperature (37°C), Histoplasma organisms transform into a yeast phase that causes a facultative intracellular infection of macrophages.
Pathogenesis
• Histoplasmosis primarily invades the lung and then spreads to the mononuclear phagocyte system (liver, spleen, etc.). The incubation period is 12 to 16 days. Widespread hemolymphatic dissemination can occur to virtually any tissue or organ system. Infection causes a granulomatous response.
• The outcome of infection is influenced by level of exposure; host cell-mediated immunity; age of the host (clinical disease is most common in young animals <4 years of age); breed (highest prevalence in sporting and hound breeds because of higher exposure risk); and immunosuppressive factors (corticosteroids may enhance dissemination).
Clinical Signs
Chronic Pulmonary Infection
Chronic pulmonary histoplasmosis is more common than the acute form and is characterized by chronic granulomatous pneumonia (diffuse or multifocal) with marked perihilar tracheobronchial lymphadenopathy that compresses the bifurcation of the trachea and mainstem bronchi. Clinical signs include chronic cough, exercise intolerance, and mild dyspnea with variable weight loss and fever. Radiographically, massive enlargement of the perihilar tracheobronchial lymph nodes and variable linear or nodular interstitial infiltrates are seen.
Intestinal Infection
• Granulomatous colitis causes bloody-mucoid large bowel diarrhea with urgency and sometimes tenesmus. If the rectum is involved, mucosal proliferations may be detected by digital palpation of the rectum.
Diagnosis
Hematology
• Normocytic-normochromic nonregenerative anemia frequently results from chronic inflammation, dissemination of Histoplasma into the bone marrow, intestinal blood loss, or hemolysis.
• Neutrophilic leukocytosis or neutropenia with a left shift and monocytosis can be seen, and occasionally pancytopenia in cats. Histoplasma organisms are occasionally seen within circulating monocytes or neutrophils on routine blood smears, especially if 1,000 cells are examined in differential cell counts or if buffy coat smears are examined.
Serum Chemistry Evaluations
• Mild hypoalbuminemia, with or without concomitant hyperglobulinemia is common in intestinal and disseminated forms. Severe panhypoproteinemia occasionally occurs in dogs with protein-losing enteropathy.
Radiography and Ultrasonography
Thoracic Radiography
• Perihilar density around the tracheal bifurcation related to tracheobronchial lymphadenopathy (especially in dogs).
Serology
• Serologic tests for histoplasmosis are unreliable; thus, every effort should be made to confirm infections through identification of the Histoplasma organisms.
Cytology
Respiratory Cytology
Use bronchoalveolar lavage, tracheobronchial washings, or fine-needle lung aspirates.
Culture
Most specimens for cytologic or biopsy identification of Histoplasma are also suitable for culture. The Histoplasma mycelial phase grows on Sabouraud’s dextrose at room temperature in 7 to 10 days, and the yeast phase grows on blood agar from 30°C to 37°C. Use a diagnostic laboratory instead of in-clinic culturing, because fungal growth is potentially infectious for humans and poses a biohazardous risk to personnel.
Treatment
• Itraconazole is the treatment of choice for histoplasmosis that is not immediately life-threatening. Treat for a minimum of 4 to 6 months and at least 1 to 2 months beyond clinical resolution.
• Itraconazole plus amphotericin B is preferred for treating severe, rapidly progressive infections, preferably using lipid-complexed amphotericin to allow higher doses with less toxicity. Combined therapy is followed by azole therapy alone for 2 to 4 months and at least 1 to 2 months beyond clinical resolution.
• Fluconazole may not be as effective as itraconazole, but it can be used for refractory ocular and neurologic infections because of its better penetration of the eyes and CNS.
• Ketoconazole is less effective than itraconazole (especially in cats), and it has more side effects; however, it can be used if other antifungal drugs are cost prohibitive for the owner. It also can be combined with amphotericin B.
BLASTOMYCOSIS
Etiology
• Blastomyces dermatitidis is a dimorphic soil-dwelling fungus with a geographic distribution in the central, mid-Atlantic, and southern Great Lakes regions of the United States, especially areas bordering the Mississippi River and its tributaries and along the St. Lawrence River region of the United States and Canada (see Fig. 20-1). The organisms reside in sandy, acidic soil near water. Most infected dogs live within ¼ mile of water.
• Inhalation of airborne spores (conidia) is the primary source of infection and leads to mycotic pneumonia. In addition, focal skin infection can occur from direct cutaneous inoculation through a wound. In tissues the fungi become budding yeast. Extrapulmonary dissemination is common in blastomycosis, especially involving lymph nodes, skin, eyes, bones, and CNS (cats). The incubation period is 1 to 3 months.
• Dogs are considered highly susceptible to blastomycosis, and the canine infection rate in endemic areas is 10 times the human infection rate. Young (<5 years) male, large-breed dogs are infected most frequently, especially pointers, hounds, and other sporting breeds, probably because of increased exposure through outdoor activities. Blastomycosis is rare in cats.
Clinical Signs
Disseminated Infection
• Cutaneous: Solitary or multiple circumscribed, raised ulcerating pyogranulomas; fistulas that drain pus or bloody fluid; deep abscesses (cats); paronychia; and regional lymphadenopathy
• Ocular: Anterior uveitis, chorioretinitis, retinal detachment, panophthalmitis, lens rupture, cataracts, secondary glaucoma, and blindness
Diagnosis
Hematology and Serum Chemistries
• Typical findings are neutrophilic leukocytosis, monocytosis, lymphopenia, and mild nonregenerative anemia.
Cytology and Biopsy
• Cytologies most often diagnostic for blastomycosis include skin impression smears, lymph node aspirates, pulmonary cytology (tracheobronchial washing, bronchoalveolar lavage, fine-needle lung aspirate), and vitreal aspirates; however, any affected tissue can be sampled. Organisms are also found in fluid specimens such as urine, prostatic washes, cerebrospinal fluid (CSF), or pleural effusion. Any routine cytology stain can be used.
• Blastomyces in tissues appear as thick-walled, extracellular yeast bodies (5-20 μm) with broad-based budding.
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